New/direct oral anticoagulants (NOAC/DOAC), like apixaban and rivaroxaban, are an interesting alternative to unfractionated or low molecular weight heparin relayed by oral anti-vitamin K anticoagulants (VKA) for the treatment of venous thromboembolism and atrial fibrillation. This new generation of anticoagulants directly inhibit a factor in the blood coagulation pathway and have a wide therapeutic range overcoming several practical issues associated with VKA therapy including the need of routine coagulation monitoring potentially simplifying patient management. However, despite this wide therapeutic range, a large interindividual dose variability related to factors such as age, body surface, smoking, concomitant diseases as well as differences in drug metabolism, could put susceptible patients at risk for uncontrolled bleeding. Both rivaroxaban and apixaban are cleared primarily via cytochrome P450 (CYP) mediated hepatic metabolism, mainly CYP3A, and renal excretion, involving the P-glycoprotein (P-gp). Both CYP3A and P-gp activity show important interindividual variations due to drug interactions and/or genetic polymorphisms in corresponding genes.

The aim of the current study is to evaluate the impact of cytochrome activity and relevant polymorphisms on rivaroxaban/apixaban dosage regimen or treatment efficacy in a hospital setting. The safety issue in this context is particularly relevant, since hospitalisation is linked to a modification of the patient's treatment with often an increase in the number of medications. The resulting changes in metabolism due to modified cytochrome and transporter activities could affect rivaroxaban/apixaban blood concentrations. Our central hypothesis is that genotype and/or phenotype in CYP3A4/5/7 or P-gp may influence the rivaroxaban/apixaban plasma concentration and increase the risk of thrombotic or hemorrhagic events. Thus, investigating how the patient's genotype and/or phenotype for CYP3A4/5/7 and P-gp could potentially alter the bio-disponibility of rivaroxaban and apixaban and therefore the risk to develop adverse events or inefficacy would be of particular interest.

Inclusion Criteria:

• Understanding of French or English language and provide signed and dated informed consent form.
• Willing to comply with all study procedures and be available for the duration of the study.
• Male or female, aged 18 years or above.
• Diagnosed with atrial fibrillation, deep-vein thrombosis or pulmonary embolism and under rivaroxaban or apixaban drug treatment.

Exclusion Criteria:

• Participation in a clinical study that may interfere with participation in this study.
• Under rivaroxaban or apixaban for prophylaxis of deep-vein thrombosis and pulmonary embolism in patients undergoing knee or hip replacement surgery.
• Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study.
• Known allergy to midazolam or to fexofenadine

Patients with atrial fibrillation, pulmonary embolism or deep-vein thrombosis, treated or on long-term prophylaxis with rivaroxaban or apixaban in a real-life clinical setting. All patients will be recruited at the Geneva University Hospitals